Work

The human 18S rRNA m6A methyltransferase METTL5 promotes tumorigenesis via DEPDC1 in lung squamous cell carcinoma

Year: 2025

Type: article

Abstract: Background N6-Methyladenosine (m6A) is one of the post-transcriptional modifications and abnormal m6A is critical for cancer initiation, progression, metastasis in Lung squamous cell carcinoma (LUSC). Ribosomal RNA (rRNA) accounts for most of the total cellular RNA, however, the functions and molecular mechanisms underlying rRNA modifications in LUSC remained largely unclear. Methods High-throughput library screening identifies the key m6A regulator METTL5 in LUSC. Cell and animal experiments were used to identify that METTL5 promoted LUSC tumorigenesis to enhance DEP domain containing 1 (DEPDC1) translation via m6A modification. Results We showed that the N6-methyladenosine (m6A) methyltransferase METTL5 was an independent risk factor in LUSC and was associated with poor prognosis of patients. Notedly, overexpression METTL5 promoted LUSC tumorigenesis in an m6A modification, while METTL5 knockdown markedly inhibited proliferation and migratory ability of tumor cells in vitro and in vivo. Mechanistically, METTL5 promoted LUSC tumorigenesis via m6a methyltransferase to increase the translation of DEPDC1. Conclusion Our results revealed that METTL5 enhances DEPDC1 translation to contribute to tumorigenesis and poor prognosis, providing a potential prognostic biomarker and therapeutic target for LUSC.

Source: Frontiers in Oncology

DOI: 10.3389/fonc.2025.1522157

Authors: Yang Yan, Jianjun Fu

Institutions: Nanchang University, First Affiliated Hospital of Jiangxi Medical College, First Affiliated Hospital of Nanchang University

Language: English

Topic: RNA modifications and cancer

Subfield: Molecular Biology

Field: Biochemistry, Genetics and Molecular Biology

Domain: Life Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,801